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Role of reactive oxygen species (ROS) within the NTS on development and maintenance of hypertension on 2 kidney-1 clip renovascular

Grant number: 14/01159-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Physiology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Eduardo Colombari
Grantee:Mariana Del Rosso de Melo
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:11/50770-1 - Neural mechanisms involved of hydroelectrolytic balance and cardiorespiratory control, AP.TEM
Associated scholarship(s):16/02091-1 - Role of the AT1R in the commissural NTS on development of renovascular hypertension, BE.EP.DR

Abstract

The high levels of blood pressure affect about 1/3 of the occidental population increasing the risk factors for coronary heart disease, stroke and heart failure. Many studies have tried to understand the causes of hypertension and the possible mechanisms that facilitate the treatment of hypertension. The central nervous system (CNS) seems to have a key role on development and maintenance of hypertension. Among the various brain areas, we can highlight the role of nucleus of solitary tract (NTS), primary site of cardiovascular afferents and which also is involved on sympathetic activity regulation in situations of hypertension. Recently, studies has showed that the oxidative stress, caused by increase on reactive oxygen species (ROS) production, might contribute to development and maintenance of hypertension. The mainly source of ROS in the CNS is the NADPH oxidase enzyme, and the isoforms NOX2 and NOX4 seems to be involved with the development/maintenance of hypertension dependent on ANG II. The proinflammatory cytokines also seems to be involved with hypertension dependent on ANG II and these cytokines can activate the NADPH oxidase. The experimental model of hypertension Goldblatt 2 kidney-1 clip (2K1C), where the hypertension developed is dependent on higher activity of renin-angiotensin system and a sympathetic hyperactivity, also depends on an increase of ROS in some areas from CNS. We recently demonstrated that the overexpression of angiotensin II (ANG II) receptors subtype AT2, which when activated have opposite effects from receptors of subtype AT1, attenuate the development of 2K1C hypertension. However we don't know if in 2K1C hypertension there is a higher ROS production into the NTS and if the NOX2 or NOX4 isoforms are involved. Thus, the objective of this study is to verify the NOX2, NOX4 and ROS expression in the NTS of 2K1C animals. Furthermore, we will study the effects of silencing these isoforms (NOX2 or NOX4) in the NTS on mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nerve activity (sSNA) of 2K1C animals. We will also study the proinflammatory cytokines in the NTS of rats with 2K1C hypertension and the effects of silencing these isoforms on cytokines proinflammatory expression and ROS production in the NTS of 2K1C animals. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MELO, MARIANA ROSSO; GASPARINI, SILVIA; SPERETTA, GUILHERME F.; SILVA, ELAINE FERNANDA; PEDRINO, GUSTAVO RODRIGUES; MENANI, V, JOSE; ZOCCAL, DANIEL B.; ALMEIDA COLOMBARI, DEBORA SIMOES; COLOMBARI, EDUARDO. Importance of the commissural nucleus of the solitary tract in renovascular hypertension. HYPERTENSION RESEARCH, v. 42, n. 5, p. 587-597, MAY 2019. Web of Science Citations: 1.

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